Polygenetic Risk Scores are used to evaluate an individual's vulnerability to developing specific diseases or conditions based on their genetic composition, by taking into account numerous genetic ...variations. This article provides an overview of the concept of Polygenic Risk Scores (PRS). We elucidate the historical advancements of PRS, their advantages and shortcomings in comparison with other predictive methods, and discuss their conceptual limitations in light of the complexity of biological systems. Furthermore, we provide a survey of published tools for computing PRS and associated resources. The various tools and software packages are categorized based on their technical utility for users or prospective developers. Understanding the array of available tools and their limitations is crucial for accurately assessing and predicting disease risks, facilitating early interventions, and guiding personalized healthcare decisions. Additionally, we also identify potential new avenues for future bioinformatic analyzes and advancements related to PRS.
Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease. Many hepatic abnormalities are associated with NAFLD such as nonalcoholic steatohepatitis, progressive ...fibrosis, cirrhosis, and liver failure. Moreover, the pathogenesis of NAFLD has numerous etiologies and can be explained due to the existence of several of stimulus that act simultaneously on genetically susceptible patients. These stimuli include obesity, diabetes, and insulin resistance. In addition, identifying the role of gut microbiota on NAFLD progression has been illustrated. In this review, we clarified the several factors that lead to the development of NAFLD and identify those who are most at risk of developing liver end-stage disease. Highlighting the noninvasive diagnostic NAFLD markers could be helpful in the disease prevention and treatment approaches.
The emerging SARS-CoV-2 variants of concern Sanyaolu, Adekunle; Okorie, Chuku; Marinkovic, Aleksandra ...
Therapeutic Advances in Infectious Disease,
2021, Letnik:
8
Book Review, Journal Article
Recenzirano
Odprti dostop
Since emerging from Wuhan, China, in December of 2019, the coronavirus (SARS-CoV-2) has been causing devastating severe respiratory infections in humans worldwide. With the disease spreading faster ...than the medical community could contain it, death tolls increased at an alarming rate worldwide, causing the World Health Organization to officially sanction the SARS-CoV-2 outbreak as a pandemic, leading to a state of worldwide lockdown for the majority of the year 2020. There have been reports of new strains of the virus emerging in various parts of the world, with some strains displaying even greater infectivity and transmissibility. Areas of the emerging variant of concern arise from countries like the United Kingdom, South Africa, Brazil, and India. These mutations carry a lineage from N501Y, D614G, N439K, Y453F, and others, which are globally dominated by clades 20A, 20B, and 20C. This literature review intends to identify and report SARS-CoV-2 variants that are currently evolving and their disease implications.
Summary
Photoprotection against excess light via nonphotochemical quenching (NPQ) is indispensable for plant survival. However, slow NPQ relaxation under low light conditions can decrease yield of ...field‐grown crops up to 40%.
Using semi‐high‐throughput assay, we quantified the kinetics of NPQ and photosystem II operating efficiency (ΦPSII) in a replicated field trial of more than 700 maize (Zea mays) genotypes across 2 yr. Parametrized kinetics data were used to conduct genome‐wide association studies.
For six candidate genes involved in NPQ and ΦPSII kinetics in maize the loss of function alleles of orthologous genes in Arabidopsis (Arabidopsis thaliana) were characterized: two thioredoxin genes, and genes encoding a transporter in the chloroplast envelope, an initiator of chloroplast movement, a putative regulator of cell elongation and stomatal patterning, and a protein involved in plant energy homeostasis.
Since maize and Arabidopsis are distantly related, we propose that genes involved in photoprotection and PSII function are conserved across vascular plants. The genes and naturally occurring functional alleles identified here considerably expand the toolbox to achieving a sustainable increase in crop productivity.
As we look so different, our genomic sequences vary enormously. The differences in our genome, genetic variations, have played very significant roles in medical research and have contributed to ...improvement of medical managements in the last 2–3 decades. Genetic variations include germline variations, somatic mutations, and diversities in receptor genes of rearranged immune cells, T cells and B cells. Germline variants are in some cases causative of genetic diseases, are associated with the risk of various diseases, and also affect drug efficacies or adverse events. Some somatic mutations are causative of tumor development. Recent DNA sequencing technologies allow us to perform single-cell analysis or detailed repertoire analysis of B and T cells. It is critically important to investigate temporal changes in immune environment in various anatomical regions in the next one to two decades. In this review article, we would like to introduce the roles of genetic variations in medical fields in the past, at present and in the future.
The genetic diversity of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) in several countries sums up to worldwide genetic diversity. In this present study, variations in terms of ...missense mutations among the SARS-CoV2 genomes from 128 Indian patients, as of May 2020, are accounted and thereby some key findings with some hypotheses were made. These mutations across various genes of these genomes show wide genetic variations in sequence and rapid evolution of SARS-CoV2 virus. The presence of unique mutations in the studied SARS-CoV2 genomes may led to their attenuation. Few Genes such as ORF6, ORF10 are free from any mutations in the Indian context of 339 genomes observed as of 14th July 2020. Further, E protein contains only one mutation. This may suggest that designing a therapeutic approach against ORF6, ORF10 and E genes may have a beneficial effect in controlling COVID-19 pandemic especially in India.
•Variations in terms of missense mutations among the SARSCoV2 genomes from 128 Indian patients, as of May 2020, are accounted and thereby some key findings with some hypotheses were made.•The presence of unique mutations in the studied SARS-CoV2 genomes has led to their attenuation. Few Genes such as ORF6, ORF10 are absolutely free from any mutations in the Indian context of 339 genomes observed as of 14th July 2020. Further, E protein contains only one mutation.•This may suggest that designing a therapeutic approach against ORF6, ORF10 and E genes may have a beneficial effect in controlling COVID-19 pandemic especially in India.
Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing ...factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.
To determine the outcomes of patients with later-onset Pompe disease (LOPD) identified through newborn screening (NBS).
A prospective observational cohort study was conducted from the initiation of ...Pompe disease NBS by following subjects every 3-12 months for motor development and biochemical markers.
Between 2005 and 2018, 39 of 994 975 newborns evaluated were classified as having LOPD based on low acid α-glucosidase (GAA) activity but no cardiac involvement at the time of screening. As of December 2020, 8 of these 39 infants (21%) were treated with enzyme replacement therapy owing to persistent elevation of creatine kinase (CK), cardiac involvement, or developmental delay. All subjects' physical performance and endurance improved after treatment. Subjects carrying c.752C>T;761C>T and c.546+5G>T; 1726G>A presented a phenotype of nonprogressive hypotonia, muscle weakness, and impairment in physical fitness tests, but they have not received treatment.
One-fifth of subjects identified through NBS as having LOPD developed symptoms after a follow-up of up to 15 years. NBS was found to facilitate the early detection and early treatment of those subjects. GAA variants c.752C>T;761C>T and c.546+5G>T; 1726G>A might not cause Pompe disease but still may affect skeletal muscle function.
•We performed integrative analysis of genetic variations DNA excision repair pathway and their association with chemosensitivity and survival outcome in AML.•ERCC8 rs158572 is deemed the most ...clinically impactful due to its association with MRD positivity and refractory group.•XPC rs2228001 is correlated with the high WBC count and overall survival (OS) of AML.
Acute myeloid leukemia (AML) is a hematologic malignancy with a high recurrence rate and poor long-term prognosis. DNA excision repair systems, such as base excision repair (BER) and nucleotide excision repair (NER), play a major role in maintaining genomic stability and integrity. Further intensive investigations are necessary to uncover additional AML prognosis loci. In this study, we analyzed 16 candidate SNPs within NER and BER pathways in AML patients. Our results showed the GT/GG genotype of the XPC rs2228001 polymorphism was significantly associated with WBC count in dominant models (OR = 0.41, 95 % CI = 0.18–0.96, p = 0.039). Additionally, the rs25487 and rs3213245 SNPs in the XRCC1 gene, in both co-dominant and dominant models, were significantly associated with PLT count in AML (p < 0.05). The GG genotype of rs1130409 in APEX1 was more prone to adverse cytogenetics in both the codominant and recessive models (p < 0.05). Furthermore, the GA genotypes of ERCC8 rs158572 in codominant model was significantly correlated with refractory group (p < 0.05). ERCC8 rs158572 and XRCC1 rs3213245 in both codominant and dominant models were significantly correlated with the MRD positivity (p < 0.05). Kaplan-Meier analysis revealed an link between overall survival (OS) and the co-dominant, dominant, and recessive models of rs2228001 in XPC. Additionally, patients with the GG and GT/GG genotype in the co-dominant, dominant model and recessive model in XPC rs2228001 exhibited significantly longer survival (p < 0.05). Multivariate Cox analyses indicated that rs2228001 in both co-dominant and dominant models were independent favorable factors impacting patient OS (OR < 1). Our findings suggest that genetic polymorphisms in DNA excision repair pathway genetic polymorphisms contribute to the chemosensitivity and prognosis of acute myeloid leukemia.
The COVID-19 pandemic has affected people worldwide with varying clinical presentations ranging from mild to severe or fatal, and studies have found that age, gender, and some comorbidities can ...influence the severity of the disease. It would be valuable to have genetic markers that might help predict the likely outcome of infection. For this objective, genes encoding VEGFR-2 (rs1870377), CCR5Δ32 (rs333), and TLR3 (rs5743313) were analyzed for polymorphisms in the peripheral blood of 160 COVID-19 patients before COVID-19 vaccine was available in Türkiye. We observed that possession of the VEGFR-2 rs1870377 mutant allele increased the risk of severe/moderate disease in females and subjects ≥65 years of age, but was protective in males <65 years of age. Other significant results were that the CCR5Δ32 allele was protective against severe disease in subjects ≥65 years of age, while TLR3 rs5743313 polymorphism was found to be protective against severe/moderate illness in males <65 years of age. The VEGFR-2 rs1870377 mutant allele was a risk factor for severe/moderate disease, particularly in females over the age of 65. These findings suggest that genetic polymorphisms have an age- and sex-dependent influence on the severity of COVID-19, and the VEGFR-2 rs1870377 mutant allele could be a potential predictor of disease severity.
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